Dose-dependent effects of folic acid on plasma homocysteine in a randomized trial conducted among 723 individuals with coronary heart disease

Nicholas Dudman, David Hunt, Stephen MacMahon, Bruce Neal, Mark Richards, John Simes, Andrew Tonkin, David Wilcken, Judy Murphy, Yvonne Cleverly, Anthony Keech, Takayoshi Ohkubo, Kathy Bos, Hazel Bartram, Derrick Bennett, Joanna Broad, Deanne Douglas, Sheila Fisher, Barry Gray, Amanda MilneAlan McCulloch, Colleen Ng, Megan Pledger, Adrienne Pryor, Aimee Santos, Alex Slater, Karen Yiu, Alan Brnabic, Mark Woodward, Louise Burrell, Louise Brown, Angas Hamer, Louise Roberts, Ian Jeffery, Pearle Taverner, Alice Kam, Philip Aylward, Fiona Wollaston, Anthony Whitehead, Geoffrey Lane, Gill Tulloch, Nicole Forrest, Jan Garrett, Greg Aroney, Pam Hicks, Jonathan Silberberg, Anne Gordon, Julie Holliday, Liz Hicks, Bhuwan Singh, Carol Singh, Judi Wilken, Bruce Jackson, Gloria Rudge, Malcolm West, Anne Carle, Thomas Marwick, Cindy Hall, David Cross, Daphne Craw, David Hunt, Michelle Sallaberger, John Horowitz, Matthew Worthley, Liz Owen, Dwain Owensby, Bill McKenzie, Julie Kesby-Smith, Suzanne MacKinley, Norman Sharpe, Robert Doughty, Jenne Pomfret, Mark Richards, Rona Buttimore, Lorraine Skelton, Michael Williams, Ralph Stewart, Marguerite McLelland, Richard Luke, Jane Kenyon, Stewart Mann, Anne Cuthbert, Stuart Reubin, Pam Yorke, Douglas Scott, Miles Williams, Renee Coxon, Darryl Fry, Malcolm Clark, Pauline Barclay, Hamish Hart, Carol O'Toole, Philippa Wright, Leigh Nairn, Jeannie Bruning

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


Aims: To determine the effects on homocysteine levels of two doses of folic acid compared to placebo, where the high dose is typical of that provided by pharmacological intervention and the low dose approximates that provided by dietary supplementation. Methods and Results: The PACIFIC study was a doubleblind, placebo-controlled, factorial randomized trial. Seven hundred and twenty-three individuals with a history of myocardial infarction or unstable angina were recruited from 28 clinical cardiology centres in Australia and New Zealand and randomized to folic acid 2·0 mg daily, folic acid 0·2 mg daily or placebo. The primary outcome, homocysteine, was measured using a fluorescence polarization immunoassay. Compared to placebo, 2·0mg folic acid reduced homocysteine by 1·8 μmol . 1 - 1 [95% confidence interval (CI) 1·3-2·3] and 0·2 mg reduced homocysteine by 1·2 μmol . 1 - 1 (95% CI 0·8-1·7). The higher dose reduced homocysteine significantly more than the lower dose (P=0·01). Conclusions: Both doses of folic acid reduced homocysteine, but the effects of the 2·0 mg dose were about one third greater than the 0·2 mg dose. Fortification of foods with folic acid should result in population-wide lower levels of homocysteine but high-dose pharmacological supplementation would produce greater reductions for high-risk individuals.

Original languageEnglish
Pages (from-to)1509-1515
Number of pages7
JournalEuropean heart journal
Issue number19
Publication statusPublished or Issued - Oct 2002
Externally publishedYes


  • Coronary heart disease
  • Folic acid
  • Homocysteine
  • Randomized trial

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this